Background Heart failure (HF) is a clinical syndrome characterized by left ventricular dysfunction or elevated intracardiac pressures. Research supports that microRNAs (miRs) participate in HF by regulating targeted genes. Hence, the current study set out to study the role of HDAC3-medaited miR-18a in HF by targeting ADRB3. Methods Firstly, HF mouse models were established by ligation of the left coronary artery at the lower edge of the left atrial appendage, and HF cell models were generated in the cardiomyocytes, followed by ectopic expression and silencing experiments. Numerous parameters including left ventricular posterior wall dimension (LVPWD), interventricular septal dimension (IVSD), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LEVDP), heart rate (HR), left ventricular pressure rise rate (+ dp/dt) and left ventricular pressure drop rate (-dp/dt) were measured in the mice. In addition, apoptosis in the mice was detected by means of TUNEL staining, while RT-qPCR and Western blot analysis were performed to detect miR-18a, HDAC3, ADRB3, cMyb, MMP-9, Collagen 1 and TGF-β1 expression patterns. Dual luciferase reporter assay validated the targeting relationship between ADRB3 and miR-18a. Cardiomyocyte apoptosis was determined by means of flow cytometry. Results HDAC3 and ADRB3 were up-regulated and miR-18a was down-regulated in HF mice and cardiomyocytes. In addition, HDAC3 could reduce the miR-18a expression, and ADRB3 was negatively-targeted by miR-18a. After down-regulation of HDAC3 or ADRB3 or over-expression of miR-18a, IVSD, LVEDD, LVESD and LEVDP were found to be decreased but LVPWD, LVEF, LVFS, LVSP, + dp/dt, and −dp/dt were all increased in the HF mice, whereas fibrosis, hypertrophy and apoptosis of HF cardiomyocytes were declined. Conclusion Collectively, our findings indicate that HDAC3 silencing confers protection against HF by inhibiting miR-18a-targeted ADRB3.
Background Patients with atrial fibrillation are at risk for ischemic stroke, even with low CHA2DS2-VASc scores. The left atrial appendage is a known site of thrombus formation in individuals with atrial fibrillation. Methods We conducted a prospective study, enrolling patients with nonvalvular atrial fibrillation and CHA2DS2-VASc scores of 0 or 1. Patients were divided into groups based on left atrial appendage morphology (determined by computed tomography): the “chicken wing” group and the non–chicken wing group. We followed patients for more than 1 year to observe the incidence of stroke. Results Of 509 patients with a mean (SD) age of 48.9 (11.6) years; 332 (65.2%) were men. The chicken wing group had fewer left atrial appendage lobes, a lower left atrial appendage depth, and a smaller left atrial appendage orifice area (all P < .001). During the follow-up period, 5 of the 133 patients (3.8%) in the chicken wing group and 56 of the 376 patients (14.9%) in the non–chicken wing group experienced ischemic stroke (P < .001). The following findings were significantly associated with the incidence of stroke: left atrial appendage depth (hazard ratio [HR], 1.98; 95% CI, 1.67-3.12; P = .03), left atrial appendage orifice area (HR, 2.16; 95% CI, 1.59–3.13; P < .001), and non–chicken wing left atrial appendage morphology (HR, 1.16; 95% CI, 1.10–1.23; P < .001). Conclusion For patients with atrial fibrillation and a low CHA2DS2-VASc score, the non–chicken wing left atrial appendage morphology type is independently associated with ischemic stroke.
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